Core Viewpoint - Immunogenic cell death (ICD) is a promising method for eliciting anti-tumor immune responses, but challenges remain in the spatial and temporal activation of tumor-specific immune responses [1][2]. Group 1: Research Development - A modular metalloprotein in situ vaccine (PPTV) has been developed for cancer immunotherapy, specifically targeting breast cancer [1]. - The research team utilized ferritin as a vaccine framework, integrating optimal mitochondrial-disrupting peptides and loading manganese ions (Mn²⁺) into its core [2]. - A prodrug strategy activated by proteases was developed to address major issues associated with ferritin, such as liver retention and drug leakage [2]. Group 2: Mechanism and Efficacy - In mouse models, PPTV effectively co-delivered mitochondrial-disrupting peptides and Mn²⁺ to tumors, triggering strong anti-tumor immune responses through ICD and the cGAS-STING pathway [2]. - The combination of PPTV with anti-PD-L1 monoclonal antibodies resulted in the eradication of established tumors, highlighting the potential of PPTV as an innovative in situ vaccine platform [2]. Group 3: Clinical Implications - The modular metalloprotein vaccine demonstrates simple preparation and safety features, indicating promising prospects for clinical translation [2].